An estimated 21 percent of the nation's 7.5 million full-time college students have used an illicit drug in the past month. Moreover, our work over the past three years has documented that concurrent nonmedical prescription drug use, other illicit drug use, and heavy drinking can all potentially affect the health, safety and well-being of college students. Unfortunately, most prior research on college students has focused solely on alcohol; the few studies on college student drug use and associated problems have had limited explanatory power or have not covered a wide scope of risk factors and consequences. Questions regarding the persistence of drug problems, (including substance use disorder) and their sequelae after college remain unanswered. This knowledge gap has severely hampered drug prevention efforts and preventive health care services for young adults. In 2003, our investigative team began an unprecedented NIDA- funded initiative to address this gap-and learn more about the natural history and consequences of illicit drug use among college students. Systematic sampling yielded a cohort of 1253 students for a longitudinal prospective study, of which 95 percent are still active in the study after 3 years of follow-up. In-depth annual interviews have yielded a rich dataset containing a wide array risk factors and outcomes. All students, regardless of academic status, are still being studied. This renewal application builds on our previous findings and proposes to continue our follow-up of this valuable cohort to answer new questions about psychosocial and physical health outcomes as they transition to adulthood. Specifically, it aims to: 1) study the persistence of drug use trajectories, including the resolution of drug problems and development of dependence; 2) understand how college drug use might interfere with achieving developmental milestones such as occupational goals and adaptive social support structures; 3) examine the reciprocal relationships over time of drug use and mental health in relation to physical health (including high-risk sexual behaviors) and quality of life; and, 4) examine potential adverse long-term consequences of cocaine and nonmedical prescription drug use, which have both significantly increased over time in our sample. This renewal offers the field a rare opportunity to probe into new transdisciplinary areas of research, and will use prospective multidimensional modeling that will take advantage of ten years of data to understand their health and functioning in the post-college period. The continuation of this study will maximize the return on NIDA's earlier investment in the project. Ultimately, the results will lead to innovative drug abuse intervention strategies, shape clinical decision-making, and improve health service delivery systems for young adults. Our ambitious and comprehensive approach ensures that this longitudinal prospective study will answer major questions about how to reduce the long-term personal and family turmoil associated with drug abuse, enable young adults to fulfill their individual potential, and reduce unnecessary economic costs to society.